Eccrine porocarcinoma

Summary

Eccrine porocarcinoma (MONDO:0006189) is a disease with 3 cohort genes and 3 clinical trials. Top therapeutic interventions include nivolumab and talimogene laherparepvec.

At a glance

• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	eccrine porocarcinoma
Mondo ID	MONDO:0006189
EFO	EFO:1000229
MeSH	D057090
DOID	DOID:7566
NCIT	C5560
SNOMED CT	254708001
UMLS	C1266065
MedGen	266098
GARD	0007431
Is cancer (heuristic)	no

Also known as: eccrine porocarcinoma · eccrine porocarcinoma of skin · epidermotropic eccrine carcinoma · malignant eccrine poroma · porocarcinoma · porocarcinoma/spiroadenocarcinoma

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › skin neoplasm › epidermal appendage tumor › sweat gland neoplasm › eccrine sweat gland neoplasm › eccrine sweat gland cancer › eccrine carcinoma › eccrine porocarcinoma

Related subtypes (5): papillary eccrine carcinoma, vulvar eccrine adenocarcinoma, malignant spiradenoma, eccrine mucinous carcinoma, ductal eccrine adenocarcinoma

Subtypes (1): vulvar eccrine porocarcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2672239	NM_005591.4(MRE11):c.668A>G (p.His223Arg)	MRE11	Uncertain significance	criteria provided, single submitter
2672240	NM_005996.4(TBX3):c.1432_1433del (p.Leu478fs)	TBX3	Uncertain significance	no assertion criteria provided
1594698	NM_003482.4(KMT2D):c.11791C>T (p.Leu3931Phe)	KMT2D	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBX3	Orphanet:3138	Ulnar-mammary syndrome
KMT2D	Orphanet:2322	Kabuki syndrome
KMT2D	Orphanet:589856	Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
MRE11	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
MRE11	Orphanet:240760	Nijmegen breakage syndrome-like disorder
MRE11	Orphanet:251347	Ataxia-telangiectasia-like disorder

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TBX3	HGNC:11602	ENSG00000135111	O15119	T-box transcription factor TBX3	clinvar
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	clinvar
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBX3	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal cortex	1
right adrenal gland	1
right adrenal gland cortex	1
buccal mucosa cell	1
medial globus pallidus	1
sural nerve	1
calcaneal tendon	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBX3	243	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, adrenal cortex
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRE11	3,932
KMT2D	3,223
TBX3	2,379

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KMT2D	O14686	11
MRE11	P49959	10
TBX3	O15119	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 71. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome	1	761.3×	0.028	KMT2D
Sensing of DNA Double Strand Breaks	1	634.4×	0.028	MRE11
STING mediated induction of host immune responses	1	346.1×	0.028	MRE11
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	317.2×	0.028	MRE11
HDR through MMEJ (alt-NHEJ)	1	292.8×	0.028	MRE11
IRF3-mediated induction of type I IFN	1	271.9×	0.028	MRE11
Diseases of DNA Double-Strand Break Repair	1	271.9×	0.028	MRE11
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	271.9×	0.028	MRE11
Resolution of D-Loop Structures	1	211.5×	0.028	MRE11
Diseases of DNA repair	1	190.3×	0.028	MRE11
DNA Double Strand Break Response	1	158.6×	0.028	MRE11
Impaired BRCA2 binding to PALB2	1	152.3×	0.028	MRE11
Activation of HOX genes during differentiation	1	146.4×	0.028	KMT2D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	141.0×	0.028	MRE11
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	141.0×	0.028	MRE11
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	141.0×	0.028	MRE11
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	131.3×	0.028	MRE11
Homologous DNA Pairing and Strand Exchange	1	126.9×	0.028	MRE11
Homology Directed Repair	1	102.9×	0.028	MRE11
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	102.9×	0.028	MRE11
Impaired BRCA2 binding to RAD51	1	102.9×	0.028	MRE11
Resolution of D-loop Structures through Holliday Junction Intermediates	1	100.2×	0.028	MRE11
HDR through Single Strand Annealing (SSA)	1	97.6×	0.028	MRE11
Meiosis	1	95.2×	0.028	MRE11
Cytosolic sensors of pathogen-associated DNA	1	95.2×	0.028	MRE11
RNA Polymerase II Transcription	2	15.0×	0.028	KMT2D, MRE11
Gene expression (Transcription)	2	11.9×	0.028	KMT2D, MRE11
Presynaptic phase of homologous DNA pairing and strand exchange	1	90.6×	0.028	MRE11
Formation of WDR5-containing histone-modifying complexes	1	88.5×	0.028	KMT2D
DNA Double-Strand Break Repair	1	82.8×	0.028	MRE11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesoderm morphogenesis	1	5617.3×	0.003	TBX3
mitochondrial double-strand break repair via homologous recombination	1	5617.3×	0.003	MRE11
beta-catenin-TCF complex assembly	1	5617.3×	0.003	KMT2D
negative regulation of cell proliferation involved in heart morphogenesis	1	5617.3×	0.003	TBX3
regulation of mitotic recombination	1	2808.7×	0.003	MRE11
limbic system development	1	2808.7×	0.003	TBX3
follicle-stimulating hormone secretion	1	2808.7×	0.003	TBX3
hepatoblast differentiation	1	2808.7×	0.003	TBX3
ureteric peristalsis	1	2808.7×	0.003	TBX3
atrioventricular bundle cell differentiation	1	1872.4×	0.004	TBX3
specification of animal organ position	1	1872.4×	0.004	TBX3
mammary placode formation	1	1872.4×	0.004	TBX3
cardiac jelly development	1	1872.4×	0.004	TBX3
oocyte growth	1	1404.3×	0.004	KMT2D
telomeric 3’ overhang formation	1	1404.3×	0.004	MRE11
luteinizing hormone secretion	1	1404.3×	0.004	TBX3
atrioventricular canal morphogenesis	1	1404.3×	0.004	TBX3
cardiac muscle cell fate commitment	1	1123.5×	0.004	TBX3
sinoatrial node cell development	1	936.2×	0.005	TBX3
female genitalia development	1	802.5×	0.005	TBX3
meiotic DNA double-strand break formation	1	802.5×	0.005	MRE11
semicircular canal morphogenesis	1	802.5×	0.005	TBX3
anterior/posterior axis specification, embryo	1	702.2×	0.005	TBX3
forelimb morphogenesis	1	702.2×	0.005	TBX3
DNA strand resection involved in replication fork processing	1	702.2×	0.005	MRE11
negative regulation of double-strand break repair via nonhomologous end joining	1	702.2×	0.005	MRE11
R-loop processing	1	561.7×	0.006	MRE11
DNA double-strand break processing	1	510.7×	0.006	MRE11
atrioventricular canal development	1	510.7×	0.006	TBX3
endocardial cushion formation	1	468.1×	0.006	TBX3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBX3	0	0
KMT2D	0	0
MRE11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MRE11	36	Binding:36
KMT2D	11	Binding:11

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	TBX3, KMT2D, MRE11

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TBX3	0	—
KMT2D	11	—
MRE11	36	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02978625	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
NCT05797415	Not specified	RECRUITING	Sentinel Lymph Node Biopsy in Ocular Surface and Adnexal Cancers
NCT03647631	Not specified	COMPLETED	Sentinel Lymph Node Biopsy in Porocarcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NIVOLUMAB	4	1
TALIMOGENE LAHERPAREPVEC	4	1